This table lists the known or suspected/predicted pharmacokinetic interactions between drugs used for the treatment or prevention of HIV-associated opportunistic infections (OIs). Many of the drugs listed in this table may also interact with antiretroviral drugs. Clinicians should refer to the drug interaction tables in the most current Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents to assess interaction potentials between OI drugs and antiretroviral therapy (ART).

Throughout the table, three recommendations are commonly used when concomitant administration of two drugs may lead to untoward consequences. The rationale for these recommendations are summarized below:

"Do not co-administer"
Indicates there is either strong evidence or strong likelihood that the drug-drug interaction cannot be managed with a dose modification of one or both drugs, and will/may result in either:

Increase in concentrations of one or both drugs, which may lead to excessive risk of toxicity; or

Decrease in concentrations of one or both drugs, which may render one or both drugs ineffective.

"Co-administration should be avoided, if possible"
There is a potential for significant pharmacokinetic interactions. However, co-administration of the drugs may be necessary if there are no other acceptable therapeutic options that provide a more favorable benefit-to-risk ratio. If other more favorable options exist, clinicians are advised to consider changing components of the regimen to accommodate a safer or more effective regimen.

"Use with caution"
Drug combinations are recommended to be used with caution when:

Pharmacokinetic studies have shown a moderate degree of interaction of unknown clinical significance; or

Based on the known metabolic pathway of the two drugs, there is a potential for pharmacokinetic interaction of unknown clinical significance.

Rifamycin-Related Interactions
Rifamycins are potent inducers of Phase I and Phase II drug metabolizing reactions. Daily doses of rifampin are well studied, and induction increases over a week or more. Based on limited data, larger doses of rifampin (e.g., 1200 mg) appear to produce the same maximum induction, but more rapidly. Single doses of rifampin may not produce significant induction. In general, rifabutin is about 40% as potent a CYP3A4 inducer as rifampin, but this can vary by substrate and enzymatic reaction. In general, daily rifapentine (for active tuberculosis [TB] disease) is at least as potent an inducer as rifampin. However, the potential of drug interactions with once weekly rifapentine (prescribed with isoniazid for latent TB infection) is not well studied, but may result in reduction of exposure of drugs that are CYP3A4 substrates. When a rifamycin is used with a potential interacting drug, close monitoring for clinical efficacy of the other agent is advised.

Co-administration should be avoided, if possible. Consider azithromycin in place of clarithromycin. If co-administered, monitor for toxicities of both itraconazole and clarithromycin (e.g., QT prolongation), consider monitoring itraconazole conc. and adjust dose accordingly.

Mefloquine

↑ Mefloquine expected

Use with caution. Consider azithromycin in place of clarithromycin. If co-administered, monitor for mefloquine toxicity (e.g., QT prolongation).

Posaconazole

↑ Clarithromycin expected

Co-administration should be avoided, if possible. Consider azithromycin in place of clarithromycin.

Quinine

↑ Quinine expected; ↑ clarithromycin possible

Do not co-administer.
Consider azithromycin in place of clarithromycin.

Use with caution. Consider azithromycin in place of clarithromycin. If co-administered, consider reducing rifabutin dose, monitoring clarithromycin and rifabutin concentrations, and monitoring for rifabutin-associated toxicities (e.g., uveitis).

Rifampina

Mean clarithromycin conc. ↓ 87%; rifampin AUC ↑ 60%

Do not co-administer. Use azithromycin in place of clarithromycin.

Rifapentinea

↓ Clarithromycin expected; ↑ 14-OH and rifapentine expected

Use with caution. Consider azithromycin in place of clarithromycin. If co-administered, monitor for rifapentine-associated toxicities, consider monitoring clarithromycin and rifapentine concentrations and adjusting doses accordingly.

Simeprevir

↑ Simeprevir expected

Do not co-administer. Consider azithromycin in place of clarithromycin.

Voriconazole

↑ Clarithromycin expected

Co-administration should be avoided, if possible. Consider azithromycin in place of clarithromycin.

Co-administration should be avoided, if possible. If co-administered, monitor for lumefantrine toxicities (e.g., QT prolongation).

Bedaquiline

↑ Bedaquiline expected

Co-administration should be avoided, if possible. If co-administered, monitor for bedaquiline toxicities (e.g., QT prolongation).

Chloroquine

↑ Chloroquine expected

Co-administration should be avoided, if possible. If co-administered, monitor for chloroquine toxicities (e.g., QT prolongation).

Clarithromycin

↑ Itraconazole and clarithromycin expected

Co-administration should be avoided, if possible. Consider azithromycin in place of clarithromycin. If co-administered, monitor for toxicities of both itraconazole and clarithromycin (e.g., QT prolongation), consider monitoring itraconazole conc. and adjusting dose accordingly.

Co-administration should be avoided, if possible. If co-administered, monitor closely for hepatotoxicity.

Erythromycin

↑ Erythromycin expected

Do not co-administer. Consider azithromycin in place of erythromycin.

Mefloquine

↑ Mefloquine expected

Co-administration should be avoided, if possible. If co-administered, monitor for mefloquine toxicities (e.g., QT prolongation).

Quinine

↑ Quinine expected; ↑ posaconazole possible

Co-administration should be avoided, if possible. If co-administered, monitor for quinine toxicities (e.g., QT prolongation).

Rifabutina

Posaconazole AUC ↓ 49%; rifabutin AUC ↑ 72%

Co-administration should be avoided, if possible. If co-administered, monitor posaconazole and rifabutin conc. and adjust doses accordingly; monitor for clinical response to posaconazole and rifabutin toxicities (e.g., uveitis).

Rifampina

↓ Posaconazole expected

Co-administration should be avoided, if possible. If co-administered, monitor posaconazole conc. and adjust dose accordingly; monitor for clinical response.

Use with caution. Consider azithromycin in place of clarithromycin. If co-administered, consider reducing rifabutin dose, monitoring clarithromycin and rifabutin conc., and monitoring for rifabutin-associated toxicities (e.g., uveitis).

Co-administration should be avoided, if possible. If co-administered, monitor posaconazole and rifabutin conc. and adjust doses accordingly; monitor for clinical response to posaconazole and rifabutin toxicities (e.g., uveitis).

Use with caution. Consider azithromycin in place of clarithromycin. If co-administered, monitor for rifapentine-associated toxicities, consider monitoring clarithromycin and rifapentine conc. and adjusting doses accordingly.

a Rifamycins are potent inducers of Phase I and Phase II drug-metabolizing reactions. Daily doses of rifampin are well studied, and induction increases over a week or more. Based on limited data, larger doses of rifampin (for example, 1200 mg) appear to produce the same maximum induction, but more rapidly. Single doses of rifampin may not produce significant induction. In general, rifabutin is about 40% as potent a CYP3A4 inducer as rifampin, but this can vary by substrate and enzymatic reaction. In general, daily rifapentine (for active TB disease) is at least as potent an inducer as rifampin. However, the potential of drug interactions with once weekly rifapentine (for latent TB infection, along with isoniazid) is not well studied, but may result in reduction of exposure of drugs that are CYP3A4 substrates. When a rifamycin is used with a potential interacting drug, close monitoring for clinical efficacy of the other agent is advised.